Prostate cancer is the most common cancer in American men and is the second leading cause of cancer death. Progress in treating human prostate cancer has been hampered by the finding that histologically identical cancers can exhibit widely variant clinical behavior. For example, in some men diagnosed with prostate cancer, the disease progresses slowly with a prolonged natural history while in other patients, disease progression can be rapid and definitive local therapy can be ineffective. The uncertainty regarding the appropriate clinical management of prostate cancer in many patients is related to an incomplete and unclear understanding of the molecular and genetic changes involved in prostate cancer development and disease progression.
A variety of clinical models or nomograms have been developed to aid clinicians with pre-treatment risk assessment. For example, since 1988, the routine use of serum prostate-specific antigen (PSA) testing in men at risk for prostate cancer has led to more favorable disease characteristics at presentation (stage migration) and earlier diagnosis and treatment. Several investigators have used these clinical parameters to stratify patients into risk groups (low, intermediate, high) and to predict clinical outcomes (Nomograms). Despite these useful parameters, approximately 30% of patients with intermediate-risk prostate cancer fail standard treatment as evidenced by a rising serum PSA following definitive therapy. A better understanding of the molecular abnormalities that define these tumors at high risk for relapse is needed to help identify more precise biosignatures.
For patients newly diagnosed with prostate cancer, there are three well-defined predictors of disease extent and outcome following treatment. These factors are clinical tumor stage (T1-T4) by digital rectal examination, Gleason score of the diagnostic biopsy specimen and serum PSA level. However, each of these factors alone has not proven definitive in predicting disease extent and outcome for an individual patient. Clinical staging by digital rectal examination may underestimate the presence of extracapsular disease extension in 30-50% of patients. Although biopsy Gleason score may be helpful in predicting pathologic stage and outcome following treatment at either end of the spectrum (i.e. Gleason 2-4 or Gleason 8-10 tumors), it is not as helpful for the majority of patients who present with Gleason 5-7 disease. As risk assessment for patients newly diagnosed with prostate cancer continues to evolve, newer tools, such as genetic or molecular determinants are needed to better predict the behavior of an individual tumor.
A need exists for large-scale discovery, validation, and clinical application of mRNA biosignatures of disease and for methods of genomic analysis in patients with established clinical prostate cancer disease to predict disease outcomes. The present invention satisfies this need and provides related advantages as well.